Continued support is requested for the NIEHS Core Center at the University of Texas Medical Branch in Galveston. During its initial 4 years, the Center has evolved to its present status as a unique entry in Southeast Texas: a scientific research center of the highest intellectual standards that is dedicated to the study of environmental health science problems, as well as to the education of our community about solutions to these problems. Our unifying theme focuses on the molecular and cellular mechanisms by which cells respond to environmental toxicants. This includes focuses on the molecular and cellular mechanisms by which cells respond to environmental toxicants. This includes the elucidation of altered DNA structures, the DNA repair mechanisms that restore the cells' original genetic integrity, and the control of gene expression and subsequent signaling pathways from toxicant challenge. Thirty Center Investigators collaborate to address this theme within the framework of two complex Research Cores. Research Core I, DNA Repair and Mutagenesis, is composed of four subcores, each focusing on a specific environmental DNA-damaging agent, including polycyclic aromatic hydrocarbons, butadiene, UV light and oxidative stress. Research Core II, Control of Gene Expression and Asthma Pathogenesis, contains two subcores that cover the regulation of gene expression in oxidative stress and signaling mechanisms in asthma pathogenesis, contains two subcores that cover the regulation of gene expression in oxidative stress and signaling mechanisms in asthma pathogenesis. A proposed third Research Core for expression in oxidative stress and signaling mechanisms in asthma pathogenesis. A proposed third Research Core for this upcoming period focuses on Biotransformation, an area in which significant faculty recruitment is in progress. To bring this scientific programs to their full potentials, a seminar program and state-of-the-art service cores have been established to facilitate collaborative research projects, enhance the scope and quality of individual Center Investigator's research, and provide access to expertise and instrumentations that could not otherwise be cost- effective. These Service Cores include the 1) Molecular Biology Core, 2) Protein Chemistry and Purification Core, 3) Synthetic Organic Chemistry Core and 4) Cell Biology Core. The NIEHS Center exists as both a force to address today's disparate and compelling human concerns about environmental health problems and the intellectual health problems and the intellectual framework that drives the research towards possible solutions. The Center focuses the environmental concerns of and develops useful programs for the local communities via the COEP, in each nearly 80% of all Center Investigators participate. From its inception, the NIEHS Center has been an integral component within a much longer UTMB program in the Environmental Health Sciences that includes a training program with centers of excellence in molecular science, structural biology, aging and oncology. Thus, the Center has become a good neighbor and responsible leader among the university, community and government entities dedicated to environmental health science problems in Southeast Texas.